PURPOSE Recently developed clinical guidelines suggest that men in families with specific cancer syndromes, such as hereditary breast and ovarian cancer (HBOC), consider genetic testing, especially in the setting of aggressive disease. However, although a family history (FH) of the same disease among close relatives is an established risk factor for prostate cancer (PC), a direct comparison of PC risk for men with each syndrome in a single population is needed. METHODS The Utah Population Database was used to identify 619,630 men, age ≥ 40 years, who were members of a pedigree that included at least 3 consecutive generations. Each man was evaluated for FH of hereditary PC (HPC), HBOC, and Lynch syndrome (LS) and for his own PC status. PC occurrences (N = 36,360) were classified into one or more subtypes: early onset (EO), lethal, and/or clinically significant. Relative risks (RRs) associated with each subtype, adjusted for important covariables, were calculated in STATA using a modified Poisson regression with robust error variances to obtain corresponding RR CIs for each FH definition. RESULTS An FH of HPC conveyed the greatest relative risk for all PC subtypes combined (RR, 2.30; 95% CI, 2.22 to 2.40), followed by HBOC and LS (both with 1 < RR < 2 and statistically significant). The strongest risks associated with FH were observed for EO disease in all pedigree types, consistent with the contribution of genetic factors to disease occurrence. CONCLUSION In this large, population-based, family database, the risk of PC varied by cancer FH and was most strongly associated with EO disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.

中文翻译：

---

与家族性和遗传性癌症综合征相关的前列腺癌风险

目的 最近制定的临床指南建议，患有特定癌症综合征（如遗传性乳腺癌和卵巢癌 (HBOC)）家族中的男性应考虑进行基因检测，尤其是在侵袭性疾病的情况下。然而，尽管近亲中同一疾病的家族史 (FH) 是前列腺癌 (PC) 的既定风险因素，但需要直接比较单个人群中患有每种综合征的男性的 PC 风险。方法 犹他州人口数据库用于确定 619,630 名年龄 ≥ 40 岁的男性，他们属于至少连续 3 代的谱系成员。每个人都评估了遗传性 PC (HPC)、HBOC 和林奇综合征 (LS) 的 FH 以及他自己的 PC 状态。PC 发生 (N = 36,360) 分为一种或多种亚型：早发型 (EO)、致死性、和/或具有临床意义。与每个亚型相关的相对风险 (RR)，针对重要的协变量进行了调整，在 STATA 中使用具有稳健误差方差的修正泊松回归计算，以获得每个 FH 定义的相应 RR CI。结果 HPC 的 FH 传达了所有 PC 亚型组合的最大相对风险（RR，2.30；95% CI，2.22 至 2.40），其次是 HBOC 和 LS（均具有 1 < RR < 2 且具有统计学意义）。在所有谱系类型中观察到 EO 疾病与 FH 相关的最强风险，这与遗传因素对疾病发生的贡献一致。结论 在这个基于人群的大型家族数据库中，PC 的风险因癌症 FH 而异，并且与 EO 疾病的相关性最强。